Wk 8- diabetic nephropathy Flashcards
Clinically diagnose diabetic nephropathy.
Officially – Biopsy – but it is hardly ever used
• Urine albumin >300mg/d (usually preceded by microalbuminuria)
• Albumin-to-creatinine ratio – corrects for dilution/concetration
Can be done by spot collection or 24 hr urine
Appropriately do a work-up for a patient with newly-diagnosed hypertension.
Assess cardiovascular risk.
Assess end organ damage.
Do labs – screening or suspected causes of hypertension.
How does diabetes mellitus lead to diabetic nephropathy? How long does this process take?
- In insulin resistance, the pancreas is forced to increase its insulin output, which stresses the β cells, eventually resulting in β-cell exhaustion.
- High blood glucose levels & high levels of saturated fatty acids => an inflammatory medium, => activation of the innate immune system, => activation of nuclear transcription factors-kappa B (NF-κB) & release of inflammatory mediators *interleukin (IL)–1β & *tumor necrosis factor (TNF)–α, => promoting systemic insulin resistance & β-cell damage as a result of autoimmune insulitis.
- Hyperglycemia & high serum levels of free fatty acids & IL-1 => glucotoxicity, lipotoxicity & IL-1 toxicity, => apoptotic β-cell death.
- Hyperglycemia also increases the expression of transforming growth factor-β (TGF-β) in the glomeruli & of matrix proteins, specifically stimulated by this cytokine.
- TGF-β & vascular endothelial growth factor (VEGF) may contribute to the cellular hypertrophy & enhanced collagen synthesis & may induce the vascular changes observed in persons with diabetic nephropathy.
- Hyperglycemia also may activate protein kinase C, which may contribute to renal disease & other vascular complications of diabetes.
*Sources say about 10 years**
Microalbuminuria typically occurs after 5 years in type 1 diabetes. Overt nephropathy, with urinary protein excretion higher than 300 mg/day, often develops after 10 to 15 years. ESRD develops in 50% of type 1 diabetics, with overt nephropathy within 10 years.
How is diabetic nephropathy related to other microvascular complications of diabetes in patients with type 1 diabetes mellitus (DM1)? How about in those with type 2 diabetes mellitus (DM2)?
- Increased Matrix production => mesangial expansion d/t hyperglycemia. (ultimately occludes glomerular capillaries=> HTN)
- Thickening of GBM (structural change-lesions develop concomitantly in the arterioles, tubules and interstitium.)
- Glomerular Sclerosis d/t HTN (Afferent Renal Artery or ischemic injury)
Another example would be diabetic retinopathy.
What is the best screening test for diabetic nephropathy? Why?
- Urine albumin (>300-500)
- Albumin-to-creatinine (20-299)
- Proteins spilling out due to damage of renal tubules
When is a renal biopsy warranted in a patient with diabetes and signs of a kidney problem?
1) Early onset proteinuria (DM1 <5yr, DM2 @ dx)
2) Nephrotic range proteinuria (>3 grams per day) – indicates they have nephrotic syndrome
3) Albumineria with the absence of retinopathy (esp in DM1)
a. DM1 – having less than 1 event is very rare
4) Presence of excellent control
a. They were diagnosed with diabetes but they reversed in HgA1c/cure (less than 5.5)
b. Still has proteinuria
c. Good control – HgbA1c (5.5-6.39?)
5) Hematuria
Who gets diabetic nephropathy? What are risk factors?
- Extremely common
- Leading cause of end-stage renal disease in the US (USRDS 2003)
- More common in African-Americans, Asians, and Native Americans than European-Americans (Young 2003); arteriosclerosis more common in Eur-Amer (even though it’s less common – it will affect them worse)
- True regardless of access to medical care
- Ultimately only ~40% of diabetics develop nephropathy
What are the usual clinical presentations of people with diabetic nephropathy?
- Early: isolate proteinuria
- Later: chronic kidney disease
- Concomitant diabetic retinopathy also increases likelihood of presence of nephropathy in setting of albuminuria
What treatments are available to prevent diabetic nephropathy in people with diabetes mellitus?
- Tight glucose control (Diabetes Control and Complications Trial Research Group 1993; Shichiri 2000)
- Nephroprotective herbs
- ACE inhibitors; ARBs (Vejakama 2012)
- Independent of blood pressure
- Blood pressure goals is a little bit lower
- Stop smoking
- Reduce BP to 130/80 mmHg or less
- Without treatment, macroalbuminuric type 1 diabetic loses 1.2 ml/min of GFR/mon on average (Viberti 1983); type 2 loses 0.5 ml/min of GFR/mon on average (Gall 1993)
Should patients with diabetic nephropathy eat low protein or low carbohydrate diets?
Low Protein (low carb wouldn’t hurt but high protein would)
What nutrients, herbs, and medications are helpful in treating patients with diabetic nephropathy?
- Thiamine, possibly Glycosaminoglyans,
• Astragalus membranaceus (astragalus) root (Li 2011)
• Rehmannia glutinosa (rehamannia) prepared root
• Angelica sinensis (dong quai) prepared root
• Codonopsis pilosula (codonopsis) root
• Actium lappa
• Silymarin
• Curcuma longa
• Vit C & E
• Alpha lipoic acid
**MEDS:
1. ACEi can prevent diabetic nephropathy —>(ACEi and ARB should not be combined)
**DM1 patients: only helpful if microalbuminuric (23–27% reduction can be expected)
***DM2 patients: helpful w/ or w/o microalbuminuric (12–21% reduction can be expected)
2. Statins- reduce diabetic nephropathy occurrence and severity.
Reduction in GFR decline by 25% with Simvastatin 40 mg qd
3. Aspirin-> No effect!
***Potential Herbal tx: CINNAMOMUM CASSIA BARK MOMORDICA DIOICA FRUIT SALVIA MILTIORRHIZA ROOT LINUM USITATISSIMUM + CUCURBITA PEPO SEEDS
What constitutes an appropriate workup for a patient with newly-diagnosed hypertension and no other signs or symptoms?
Think about renal issues – therefore, perform tests that deals with the kidney
How is the plasma renin activity test interpreted? Aldosterone test? The ratio between the two?
*Volume Hypertension
(Low-Renin: Hypertension, Aldosteronism, Aldosterone dominance)
*Renin Hypertension
*Plasma renin activity (PRA)
<0.65 ng/ml/hr –>HTN
>0.65 ng/ml/hr –>Renal Art. Stenosis
*Direct Renin
(less accurate)
<5 mU/ml
>5 mU/ml
- Main etiology
1. Sodium-volume, r/o adrenal adenoma & hyperaldosteronism*
2. Renin-angiotensin-induced vasoconstriction/inflammation
*Frequency
33% of patients
More common in elderly, blacks and Hispanics-> 67% of patients
- *Drugs indicated
1. thiazide diuretic
2. calcium channel blocker
3. alpha blocker (increases mortality though)
4. aldosterone inhibitor eg (spironolactone, eplerenone, mineralocorticoid receptor antagonist)
5. angiotensin-converting enzyme inhibitor (ACEi)
6. angiotensin receptor blocker (ARB)
7. beta blocker
***Drugs contraindicated
Glycyrrhiza
diuretics
How common is renal artery stenosis and how is it diagnosed?
Rare
• Secondary: renin activity elevated (normal or low in primary) >3.7 ng/ml * hr
• PRA >0.65 ng/ml/h
• 67% of patients who have htn
How is hypertensive nephropathy best prevented?
Volume hypertension: Low sodium diet
Renin hypertension: whole foods diet
